Rheumatoid arthritis is an autoimmune disease associated w/the MHC Class II marker HLA-SR4. This observation and other data suggest an important pathogenic role for T cell-mediated presentation of an autoantigen in the context of HLA-DR4. Self-peptides which are presented to T cell receptors may perpetuate the aberrant immune response characteristic of this chronic disease. Intervention to induce selective energy or apoptosis of activated autoreactive T cells could have therapeutic benefit. The construct being tested utilizes a peptide derived from human cartilage glycoprotein 39 (Hcgp39) which induces arthritis in mice. Vaccination of individuals w/the appropriate MHC Class II marker complexed w/HCgp39 is proposed as a method for induction of specific immune unresponsiveness. SPECIFIC AIMS: Patients w/RA will be treated w/the MHCII: Peptide complex containing Hcgp39 and DR4, designated AG4263, in a double blind, multicenter trial. The primary objective is to evaluate safety and tolerability of an induction course and one maintenance cycle of AG4263. The secondary objectives are to evaluate the biological effects of AG4263, to obtain pharmacokinetic data and to get a preliminary assessment of effects on disease activity.